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Hereditary Pheochromocytoma-Paraganglioma

Familial Pheochromocytoma-Paraganglioma

Hereditary pheochromocytoma-paraganglioma is a term encompassing several distinct genetic disorders in which the two respective tumors appear. Mutations in succinate dehydrogenase (SDH) genes seem to play a pivotal role in the pathogenesis. Typical manifestations arise from excessive catecholamine secretion - hypertension, headaches, diaphoresis, anxiety, and palpitations are some of the most common. The detailed patient history, physical examination, biochemical tests, and imaging and genetic studies should be used to make an early diagnosis as a significant risk exists toward a malignant transformation of tumors and their metastatic spread.


The clinical presentation of hereditary pheochromocytoma-paraganglioma mainly depends on the secretory properties of the two tumors. A pheochromocytoma, arising from the adrenal medulla, almost always secretes catecholamines, whereas paragangliomas (arising from paravertebral neuroendocrine tissues) can be either parasympathetic and nonsecretory, or sympathetic and produce catecholamines as well [1] [2] [3] [4]. The main feature of catecholamine hypersecretion is paroxysmal hypertension, which is encountered in virtually all patients [1] [2] [4] [5]. Palpitations, tachycardia, arrhythmia, headaches, bouts of diaphoresis, and anxiety attacks are other frequent manifestations of this disease [1] [2] [5]. These manifestations are often induced when the individual changes his/her body position (for example, from sitting to standing) but surgery, exercise, and drug-induced manipulations of blood pressure may also serve as promoting factors [1] [3] [5]. Painless hematuria could be observed if paragangliomas are located within the urinary bladder wall [1]. On the other hand, the cranial or neck localization of paragangliomas can result in a unilateral hearing loss, tinnitus, dysphagia, localized pain, impaired tongue movement, or even cough or hoarseness due to the mass effect of the spreading tumor [1]. Head and neck paragangliomas, however, are rarely secretory and are much less likely to produce catecholamine-related symptoms [1] [3] [4] [5].

Localized Pain
  • On the other hand, the cranial or neck localization of paragangliomas can result in a unilateral hearing loss, tinnitus, dysphagia, localized pain, impaired tongue movement, or even cough or hoarseness due to the mass effect of the spreading tumor.[symptoma.com]
  • Incorporation of rigorous quality control steps throughout the workflow of the pipeline ensures the consistency, validity and accuracy of results. Our pipeline is streamlined to maximize sensitivity without sacrificing specificity.[blueprintgenetics.com]
  • […] phenotypes Inheritance ClinVar HGMD FH Hereditary leiomyomatosis and renal cell cancer AD/AR 178 207 MAX Pheochromocytoma AD 13 31 NF1 * Watson syndrome, Neurofibromatosis, Neurofibromatosis-Noonan syndrome AD 1157 2901 RET Hirschsprung disease, Central hypoventilation[blueprintgenetics.com]
Muscular Atrophy
  • Arkblad EL, Darin N, Berg K, Kimber E, Brandberg G, et al.. (2006) Multiplex ligation-dependent probe amplification improves diagnostics in spinal muscular atrophy. Neuromuscul Disord 16: 830–838. Epub 2006 Oct 2017. 32.[journals.plos.org]
Retinal Damage
  • For example, children are susceptible to visual loss as result of retinal hemangiomas that, in the absence of surveillance, may go unnoticed until retinal damage becomes severe.[clincancerres.aacrjournals.org]
Hearing Impairment
  • Complete Probemix List New and Improved Products IVD-Registered Products Bacteria Blood Cancers Cardiovascular Carrier Endocrine & Reproductive Gastrointestinal & Liver Hearing Impairment Hereditary Blood Disorders Immunological Imprinting Intellectual[mlpa.com]
  • Palpitations, tachycardia, arrhythmia, headaches, bouts of diaphoresis, and anxiety attacks are other frequent manifestations of this disease.[symptoma.com]
  • We experienced an 18-year-old woman who complained of severe headaches in whom hypertension was revealed. She was suspected of having a malignant tumor based on her clinical characteristics, despite showing no evidence of metastatic lesions.[ncbi.nlm.nih.gov]
  • The doctor should pay special attention to symptoms such as high blood pressure, heart palpitations, anxiety, headache, coughing, hoarse voice, problems swallowing and hearing loss.[stjude.org]
  • Hypersecretion manifests as sustained or paroxysmal elevations in blood pressure, headache, episodic profuse sweating, palpitations, pallor and apprehension or anxiety.[orpha.net]
  • The medical history should include symptoms of catecholamine excess, such as elevation in blood pressure, headaches, diaphoresis, and palpitations, and also symptoms attributable to mass effect, such as dysphagia, hearing loss, and dysarthria.[clincancerres.aacrjournals.org]


Because of the potential for malignant transformation of both pheochromocytomas and paragangliomas in this hereditary syndrome, it is critical to establish an early diagnosis. With a properly obtained patient history and a detailed physical examination, the physician can obtain sufficient information to indicate further testing. In addition to the onset of symptoms, as well as their course and progression, the patient interview might reveal incompletely explained sudden death within the family, which may favor a hereditary component in the presumptive diagnosis [1]. During the physical examination, tachyarrhythmia and blood pressure changes can be observed [1].

Imaging studies are the cornerstone in recognizing the etiology of the disease. Computed tomography (CT) and magnetic resonance imaging (MRI) are the two main imaging procedures that are able to visualize the tumor location [1] [2]. MRI, but also 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/CT scanning and 123I-metaiodobenzylguanidine (MIBG) scintigraphy are used for the detection of metastatic disease [1] [2].

Biochemical studies should be carried out to determine the concentration of catecholamines in the circulation. Measurements of serum free or urinary fractioned metanephrines through liquid chromatography-mass spectrometry (LC-MS) is regarded as the optimal laboratory procedure [2].

Finally, a distinction between different disorders where these two tumors appear is achieved through genetic studies. Revealed mutations of specific succinate dehydrogenase (SDH) genes are main criteria used to confirm the diagnosis of hereditary pheochromocytoma-paraganglioma [5] [6].

Multiple Renal Cysts
  • renal cysts The type of variant identified in the VHL gene has been shown to account for differences in PHEO risk, with a strong genotype–phenotype correlation ( Table 1 ; ref. 17 ).[clincancerres.aacrjournals.org]


  • Management and treatment Treatment for secreting tumors involves blood pressure control with alpha-blockers followed by surgery by specialized teams. If the tumors have not metastasized, surgical resection can be curative.[orpha.net]
  • Make the best clinical decisions with an enhanced emphasis on evidence-based practice and expert opinions on treatment strategies. Zero in on the most relevant and useful references with the aid of a more focused, concise bibliography.[books.google.de]
  • HanX Biopharmaceuticals acquired the rights in Greater China to rigosertib, a new drug candidate Bucks County-based Onconova is developing initially as a treatment for patients at higher risks for developing myelodysplastic syndromes of MDA.[medworm.com]
  • [PUBMED Abstract] Regional Pheochromocytoma Treatment The standard treatment option for regional pheochromocytoma is surgery.[cancer.gov]
  • When clinical trials show that a new treatment is better than the standard treatment, the new treatment may become the standard treatment. Patients may want to think about taking part in a clinical trial.[northshore.org]


  • The present case indicates that conducting genetic testing, including SDHB mutation analyses, is required to determine the prognosis in patients highly suspected of having HPPS.[ncbi.nlm.nih.gov]
  • Prognosis The disease may be fatal, but some have lived with malignant PCC/PGL for 20 years or more. The documents contained in this web site are presented for information purposes only.[orpha.net]
  • When that person’s short-term prognosis is poor, or their health is unstable, urgent storage of a blood sample may be prudent. The goal of storing a blood sample is to allow for the possibility of hereditary cancer genetic testing in a family.[bccancer.bc.ca]
  • 雑誌 Eur J Endocrinol 171:R111-22 (2014) DOI: 10.1530/EJE-14-0113 文献 PMID: 22851969 (description, gene, marker, drug, tumor type) 著者 Parenti G, Zampetti B, Rapizzi E, Ercolino T, Giache V, Mannelli M タイトル Updated and new perspectives on diagnosis, prognosis[genome.jp]


  • Imaging studies are the cornerstone in recognizing the etiology of the disease. Computed tomography (CT) and magnetic resonance imaging (MRI) are the two main imaging procedures that are able to visualize the tumor location.[symptoma.com]
  • Etiology Up to 10% of genetically determined PCC/PGLs are due to a SDHx germline mutation.[orpha.net]
  • In general, this test is used when a patient's medical history and family history findings strongly suggest that there is an underlying genetic etiology of paragangliomas and/or pheochromocytomas.[bcm.edu]
  • Succinate Dehydrogenase (SDH)-Deficient Pancreatic Neuroendocrine Tumor Expands the SDH-Related Tumor Spectrum This study strengthens the etiological association of SDH genes with pituitary neoplasia, renal tumorigenesis, and gastric gastrointestinal[sdhcancer.org]
  • The etiology of the Carney triad syndrome is unknown; no candidate gene has been discovered until now and the disease does not appear in a family pattern.[frontiersin.org]


  • Summary Epidemiology Hereditary PGL/PCCs represent 30% of all PGL/PCC, for which prevalence is around 1/500,000 for PCC and 1/1,000,000 for PGL.[orpha.net]
  • When comparing the incidence and mortality rates of PC, the Surveillance Epidemiology and End Results data of 2005-2014 show that Appalachian Kentucky had a lower incidence (113/100 000 v 137/100 000) but a higher mortality rate (23.8% v 21.8%) when compared[medworm.com]
  • Elements of cancer epidemiology. Chemical and environmental carcinogenesis. Concepts of tumor initiation and promotion. Principal direct and indirect chemical carcinogens, their modes of action and risk factors.[unich.it]
  • Linguistic Variant - Portuguese, Brazil) 2015AB LNC-RU-RU (LOINC Linguistic Variant - Russian, Russia) 2015AB LNC-TR-TR (LOINC Linguistic Variant - Turkish, Turkey) 2015AB LNC-ZH-CN (LOINC Linguistic Variant - Chinese, China) 2015AB MCM (Glossary of Clinical Epidemiologic[doctor.am]
  • Epidemiology and clinical characteristics 2.1.[intechopen.com]
Sex distribution
Age distribution


  • Pathophysiologically, an impaired ability of intracellular oxygen sensing might be involved in tumorigenesis, resulting in constant signaling of hypoxia in the cell.[em-consulte.com]
  • Evolving concepts in the pathophysiology, diagnosis and treatment of pheochromocytoma. Endocr Rev 1994; 15 :356–368. 43. Shapiro B, Sisson JC, Lloyd R, et al. Malignant pheochromocytoma: clinical, biochemical and scintigraphic characterization.[nature.com]
  • Genetic pathways and pathophysiology of mutations The genetic origin influences the natural history of NETs.[intechopen.com]


  • Cancer screening/surveillance protocols Early recognition and testing of at-risk individuals is key to the prevention of morbidity and mortality in vHL.[clincancerres.aacrjournals.org]
  • […] counselors dedicated to providing patients with access to personalized hereditary risk evaluation, genetic testing, recommendations for screening and prevention, and long-term follow-up.[dana-farber.org]
  • NCI_CTEP-SDC (Cancer Therapy Evaluation Program - Simple Disease Classification) 2015AB NCI_CareLex (Content Archive Resource Exchange Lexicon) 2015AB NCI_DCP (NCI Division of Cancer Prevention Program) 2015AB NCI_DICOM (Digital Imaging Communications[doctor.am]
  • Clinical Actionability Tools Clinical Actionability tools support the curation process is to identify those human genes that, when significantly altered, confer a high risk of serious disease that could be prevented or mitigated if the risk were known[clinicalgenome.org]
  • At the moment there is no known preventive surgical approach that can significantly improve outcomes in MEN1 patients, with the exception of prophylactic thymectomy to prevent the occurrence of the rare thymic carcinoid tumor, a tumor frequently malignant[intechopen.com]



  1. Kirmani S, Young WF. Hereditary Paraganglioma-Pheochromocytoma Syndromes. 2008 May 21 [Updated 2014 Nov 6]. In: Pagon RA, Adam MP, Ardinger HH, et al., eds. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
  2. Lenders JW, Duh QY, Eisenhofer G, et al. Pheochromocytoma and paraganglioma: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2014;99:1915–1942.
  3. Lefebvre M, Foulkes WD. Pheochromocytoma and paraganglioma syndromes: genetics and management update. Curr Oncol. 2014;21(1):e8-e17.P
  4. Pasini B, Stratakis CA. SDH mutations in tumorigenesis and inherited endocrine tumours: lesson from the phaeochromocytoma–paraganglioma syndromes. J Intern Med. 2009;266:19–42.
  5. Fishbein L, Nathanson KL. Pheochromocytoma and Paraganglioma: Understanding the Complexities of the Genetic Background. Cancer Genet. 2012;205(1-2):1-11.
  6. Gill AJ, Pachter NS, Clarkson A, et al. Renal tumors and hereditary pheochromocytoma-paraganglioma syndrome type 4. N Engl J Med. 2011;364(9):885-886.

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Last updated: 2019-07-11 19:57